Apparatus for the preparation of a radioactive aqueous solution

ABSTRACT

A device for preparing a radioactive water solution to be infused in a patient includes a reaction chamber ( 13 ) in which radioactive water vapour is formed by the catalysed reaction of oxygen gas containing oxygen-15 and hydrogen gas. A diffusion chamber ( 14 ) is provided which allows the radioactive water to penetrate, but which prevents the penetration of gasses. Tubes ( 26 ) and valves ( 16, 18 ) direct a sterile saline solution to the diffusion chamber ( 14 ), and then direct the saline solution containing radioactive water out from the diffusion chamber to a patient, or to a decay coil ( 22 ) being a part of the device. A measuring instrument is provided for measuring the radioactivity of the radioactive solution. The device is characterized in that the diffusion chamber ( 14 ), the tubes ( 26 ) the valves ( 16, 18 ), the radioactivity measuring instrument ( 17 ), and preferably also the reaction chamber  913 ), are mounted in the same frame  50 , whereby they form a separate unit i.e. a water module ( 30 ), which as one entity can be detached from the lead shield ( 10 ) surrounding the device.

This application is a National Stage Application of PCT/F100/00408,filed May 9, 2000.

The object of the invention is a device for preparing a radioactivewater solution to be infused in a patient.

Positron emission tomography (PET) is a quantitative, functional isotopeimaging method used, for instance, for the examination of bloodcirculation in the human heart, brain or skeletal muscles. Waterlabelled with the short-lived (half-life 2.05 minutes) oxygen-15-isotopeis used as the radioactive tracer. The radioactive water is administeredas a physiological sodium chloride solution in water.

In order to examine a patient's blood circulation a radioactive solutionwill be infused, the solution comprises a physiological saline solution,in which radioactive water has been mixed, where oxygen is theradioisotope 15_(O) (oxygen-15). According to prior art such a solutionis prepared in a device according to FIG. 1. Radio-active gas containing1% oxygen and 99% nitrogen is supplied via the opening 11 in the leadshield of the device surrounded by the lead shield 10. A part of thetotal oxygen is non-radioactive oxygen, and a part is radioactive oxygen(oxygen-15). The radioactive gas is generated in a cyclotron. From asecond opening 12 mixing gas is supplied into the device, the mixing gascontaining 5% hydrogen and 95% nitrogen. By the catalyzed reaction ofthe hydrogen of the mixing gas with the oxygen of the radioactive gas ina reaction chamber (“oven”) 13 radioactive water vapour is generated.The reaction is carried out in the presence of a palladium catalyst, thetemperature is usually maintained at about 200° C. by electrical heatingThe gas coming from the reaction chamber 13 and containing radioactivewater vapour is directed into a diffusion chamber 14 having asemi-permeable membrane (which usually is a dialysis membrane). Asterile saline solution is pumped via the opening 15 and the valve 16into the diffusion chamber above the semi-permeable membrane. Theradioactive water vapour penetrates the membrane and mixes into thesterile saline solution. Then the solution is directed to aGeiger-Muller counter 17 to measure the radioactivity, after which it isdirected through the valve 18 and the opening 19 to the patient. Thesolution is administered intravenously into the patient for the PETexamination. The valves 16 and 18 are three-way membrane valves. Thereference numbers 20 and 21 represent filters. The radioactive watercannot be stored as the half-life of the oxygen-15 isotope is only 2.05minutes, therefore it must be fresh when it is supplied to the patient.Patient examinations are not made continuously, but the operation of thecyclotron must be continuous.

Thus the preparation of the radioactive water is continuous, whereas itsuse is random. The waste production of radioactive saline solution isdirected into a decay coil 22 for removal of the radioactivity, afterwhich the solution is discharged via the opening 23. The gas which doesnot penetrate the membrane of the diffusion chamber is discharged fromthe device via the opening 24. The device is arranged in a lead shieldin order to avoid irradiating the surrounding environment. The itemnumber 25 shows a lead plug. The device which including its lead shieldweighs several hundred kilograms is mounted under or on one side of thebed of the patient to be examined.

However, some disadvantages relate to the device described above. Alltubes (26) and valves (16, 18) as well as the diffusion chamber arepermanently mounted in the device. The device is installed in a leadchamber, which is quite heavy and thus difficult to move on wheels andcumbersome to open. The saline solution generated by the device andbeing dispensed must be sterile and free of pyrogens, and therefore thedevice must be tested for pyrogens each day. Further the device has arisk of virus contamination, because in principle an infection could getfrom the patient into the device as the result of a reverse flow.

The object of this invention is to provide an improved device forpreparing a radioactive water solution intended for infusion in apatient, the device being easy to dismount and where the componentscoming into contact with the saline solution are easy to replace. Aparticular object is to provide a device where the sterility problemsand the risk of contamination are eliminated. A further object is toprovide a device where electrical safety is better than in knowndevices.

The characteristics of the invention appear in the claims. A deviceaccording to the invention is characterised in that the diffusionchamber, tubes, valves, radioactivity measuring instrument, andpreferably also the reaction chamber, are mounted in the same frame andform a separate unit, i.e. a water module, which as one unit can bedetached from the lead shield surrounding the device.

The invention is described in more detail with the aid of the followingfigures, in which

FIG. 1 shows a device according to prior art;

FIG. 2 shows a device according to the invention as a flow diagram; and

FIGS. 3A and 3B show the modular structure of a device according to oneembodiment of the invention.

FIG. 2 shows the different components of the device when they areconnected to each other. The radioactive gas from the cyclotroncontaining 1% oxygen, a part of which is radioactive oxygen (oxygen-15),and 99% nitrogen, and a mixing gas containing 5% hydrogen and 95%nitrogen, are supplied to the reaction chamber 13 where the hydrogen andthe oxygen undergo catalytic reaction in the presence of a Pd/Al₂O₃catalyst to form water vapour. The temperature of the reaction chamberreaches 100 to 110° C., the heat being generated by the reaction of theoxygen and hydrogen. Due to this relatively low temperature thegeneration of ammonia is avoided. By using a smaller amount (300 mg) ofa suitable catalyst (e.g. 1.0% Pd on alumina) radioactive water has beenobtained at a yield which is 25 to 30% higher than in a conventionalreaction chamber. The use of the previously predominant electricalheating of the reaction chamber with a resistor has been abandoned, andthis has not reduced the yield of radioactive water. The reactionchamber 13 is connected to the diffusion chamber 14 by quick connects,in which case the distance between the reaction chamber and thediffusion chamber is very short (about 15 mm). The temperature of thereaction chamber is sufficiently high to keep the radioactive watergenerated in it in the form of steam when it enters the diffusionchamber. The diffusion chamber 14 has two membranes 14 a and 14 b, whichseparate the gas phase 40 from the liquid phase 41. The upper membrane14 a which is in contact with the gas phase 40 is a hydrophobic membrane(for instance of the type Millipore GV), and the lower membrane 14 bwhich is in contact with the liquid phase 41 is a hydrophilic membrane(for instance of the type Millipore GS). Sterile sodium chloridesolution is supplied by an infusion pump (not shown in the figure) tothe solution side 41 of the diffusion chamber. The radioactive watervapour which has penetrated the membrane 14 a will condense and mix withthe sterile saline solution in the space between the membranes 14 a and14 b of the diffusion chamber. The hydrophilic membrane 14 b effectivelyprevents the penetration of gases, and they are discharged as wastegases. The radioactive saline solution is supplied via the valve 16passed the photodiode 17 acting as a radioactivity measuring instrument,after which it is directed via the valve 18 to the patient, or to thedecay coil 22, if there is no patient to be examined.

FIG. 3B shows in a cross section the structure of a device according tothe invention. Within the lead shield 10 provided with an easily openedlid 10 a there is a device which comprises a decay coil 22, into which aso called water module 30 can be inserted. Air cushions (not shown inthe figure) are arranged under the lead shield, so that the equipmentcan be easily moved, even if it weighs several hundreds of kilograms.Preferably the lead shield 10 is provided with a small hole of about 20mm diameter, to which a pipe is connected (not shown in the figure),which pipe could be connected to an extraction system. If there are anygas leaks from the device, such as leaks of unreacted hydrogen orradioactive gas, it is desirable that the lead shield be connected to anextraction system, so that these gases endangering safety can not spreadinto the immediate surroundings of the device.

The position of the water module 30 is marked with broken lines in FIG.3B. In connection with the decay coil unit there are mounted quickrelease connectors “quick connects” 31 b for the gases and for the wasteliquid i.e. the liquid going to the decay coil. Further in connectionwith the decay coil unit there is an electric connector for thecomponents of the water module which require electricity, such as forthe valves 16 and 18 and the photodiode 17. FIG. 3A shows the watermodule 30 when it is detached from the lead shield 10 and the decay coil22 of the device. The water module 30 comprises a frame 50, in which thefollowing components are mounted in this solution: a diffusion chamber14, tubes (not shown in the figure), valves 16 and 18, a radioactivitymeasuring instrument 17, and a reaction chamber 13. The water module 30contains “quick connects” 31 a for the gases at and for the liquid goingto the decay coil (the waste liquid) and an electric connector 32 a forthe components of the water module requiring electricity. Theseconnectors are connected to the connectors 31 b and 32 b in connectionwith the decay coil unit. The valves 16 and 18 are pinch valves or thelike, which do not come into contact with the liquids flowing in thetubes.

Significant advantages are achieved with a module structure like this.As the diffusion chamber and the tubes transporting liquids are arrangedin a separate module which can easily be detached from the lead shield,and as the valves are of the type which do not come to contact with theflows of liquid they direct, the diffusion chamber and the liquid tubescan be replaced after each patient treatment. The replaced componentscan be disposable, or they can be sterilised and reused. With thisarrangement it can be ensured that the liquid delivered to the patientis sterile. The risk of contamination and the tests for pyrogens areavoided. Regarding the module structure it is most important that itcomprises a diffusion chamber, valves, tubes and the radioactivitymeasuring instrument. As the reaction chamber is rather small, it canalso easily be placed in the module, in the manner shown in FIG. 3A.

The electric safety of the device is substantially improved byabandoning the electric heating of the reaction chamber and by using aphotodiode instead of a Geiger Muller counter as the detector of theradioactivity. The voltage required by a photodiode is 12 V, while thevoltage required by a Geiger Muller counter is about 300V.

By using two membranes in the manner shown above it ensures that gasbubbles cannot get into the liquid to be infused.

The embodiments of the invention mentioned above are only examples ofhow the inventive idea can be realised. To a person skilled in the artit is obvious that different embodiments may vary within the scope ofthe claims presented below.

1. A device for preparing a radioactive water solution to be infused ina patient and which is adapted to be mounted detachably to a surroundinglead shield, the device comprising: a reaction chamber (13) within whichradioactive water is capable of forming by catalytic reaction ofhydrogen gas with radioactive oxygen-15 gas; a diffusion chamber (14)which allows the radioactive water to penetrate, but which prevents thepenetration of gases; tubes (26) and valves (16, 18) for directing asterile saline solution to the diffusion chamber (14), and for directingthe saline solution containing radioactive water out from the diffusionchamber; a measuring instrument (17) for measuring the radioactivity ofthe radioactive solution, and a frame (50) for commonly mounting atleast the diffusion chamber (14), the tubes (26), the valves (16, 18)and the radioactivity measuring instrument (17), to form a separatewater module unit (30), which as one entity is capable of being detachedfrom the lead shield (10) surrounding the device.
 2. A device accordingto claim 1, further comprising a decay coil (22), wherein the watermodule unit (30) is separable from the decay coil (22).
 3. A deviceaccording to claim 2, wherein water module unit (30) and the decay coil(22) comprise mateable quick release connectors (31 a, 31 b) for thegases and the liquid directed from the water module unit (30) to thedecay coil (22), and an mateable electric connectors (32 a, 32 b) forthe components of the water module unit requiring electrical supplies.4. A device according to claim 1, wherein the tubes (26) of the watermodule unit (30) conveying the saline solution to the diffusion chamber(14) are replaceable after each patient examination, and wherein thevalves (16, 18) are pinch valves which do not come into contact withliquids flowing in the tubes.
 5. A device according to claim 1, whereinthe diffusion chamber (14) comprises two membranes (14 a, 14 b) locatedon respective gas and saline solution sides thereof, wherein a first oneof the membranes (14 a) is a hydrophobic membrane located on the gasside (40), and a second one of the membranes (14 b) is a hydrophilicmembrane located on the saline solution side (41).
 6. A device accordingto claim 1, wherein the radioactivity measuring instrument (17)comprises a photodiode.
 7. A device according to claim 1, wherein thereaction chamber (13) is a small-size reaction chamber operatingexclusively with the aid of the heat of the reaction between oxygen andhydrogen.
 8. A device according to claim 1, wherein the frame (50) alsocommonly mounts the reaction chamber (13) as part of the water moduleunit.
 9. A system for providing a radioactive water solution to beinfused in a patient comprising a device in which the radioactive watersolution is prepared, and a lead shield (10) which surrounds the device,wherein the device comprises: a reaction chamber (13) within whichradioactive water is capable of forming by catalytic reaction ofhydrogen gas with radioactive oxygen-15 gas: a diffusion chamber (14)which allows the radioactive water to penetrate, but which prevents thepenetration of gases; tubes (26) and valves (16, 18) for directing asterile saline solution to the diffusion chamber (14), and for directingthe saline solution containing radioactive water out from the diffusionchamber to a patient or to a decay coil (22) a measuring instrument (17)for measuring the radioactivity of the radioactive solution, and a frame(50) for commonly mounting at least the diffusion chamber (14), thetubes (26), the valves (16, 18), and the radioactivity measuringinstrument (17), to form a separate water module unit (30), which as oneentity is detachably mounted to the lead shield (10) surrounding thedevice; and wherein the lead shield (10) of the device is provided witha lid (10 a) which can be easily opened.
 10. A device system accordingto claim 9, further comprising are cushions which are arranged under thelead shield (10).
 11. A system according to claim 9, the lead shield(10) a hole and a tube connected to the hole, wherein the tube isconnectable to a suction source.